Genetic variability of the V1 and V2 env domains of SIVcpz-ant and neutralization pattern of plasma viruses in a chimpanzee infected naturally

Specific neutralizing epitope changes have been observed in a chimpanzee in fected naturally with SIVcpz, which differ from HIV-1 infecting humans. To characterize further these changes, a longitudinal study of env genomic seq uence variation of SIVcpz-ant isolates was undertaken in this animal. The V 1 and V2 regions of the env were determined to arise from specific recombin ation events. To determine whether recombination of the V1 and V2 domains w as possibly associated with the emergence of neutralization escape viruses, envelope sequences and gene length polymorphisms from PBMC and plasma vira l variants were studied over a 7-year period. PBMCs and plasma-associated i nfectious virus titers as well as plasma RNA viral loads were monitored lon gitudinally. The first 5 viruses isolated from the plasma were found to be neutralization escape variants. Sequence ana sis of their V1 and the V2 reg ions indicated that a 20 amino acid stretch of the V1 region h undergone re combination and was also associated with the emergence of isolates elicitin g strong neutralization responses. These findings support the hypothesis th at recombination of the V1 and V2 regions of the envelope play a role in ne utralization escape of SIVcpz in chimpanzees infected naturally. Furthermor e, the data confirm that the neutralizing antibody response plays an import ant role in the decline of plasma infectious virus titers in HIV-1 related SIVcpz nonpathogenic infection. (C) 2001 Wiley-Liss, Inc.